: The Goal of this project is to develop improved hardware, software and specimen preparation techniques to make the automated karyotyping of human cells significantly faster, more accurate, and easier to interpret by using multicolor chromosome painting probes and multispectral image analysis. In phase I, the investigators will evaluate combinatorial and ratio labeling and the use of DNA obtained from somatic cell hybrids and from microdissection. Ultimately they will develop fluorescence in situ hybridization (FISH) specimen preparation techniques to label uniquely all 24 human chromosome types using mixtures of fluorophores in chromosome painting probes. They propose to develop an instrument with a special multispectrual CCD camera and new image analysis software to identify the homologue origin of DNA by color alone. Combined with conventional morphological and banding information this is intended to produce a near- error-free karyotype, significantly reducing the operator time required for interactive error correction and thereby increasing the instrument's throughput rate. The color karyotype will show numerical and gross structural abnormalities, and the image analysis will flag translocations of genetic material, further assisting diagnosis. The investigators will test the system on postnatal and cancer specimens from bone marrow and peripheral blood. When fully developed, the new technology will be integrated into IRIS's existing line of cytogenetics automation products. This will result in commercial instruments that are more effective in automated karyotyping and can more accurately detect and elucidate small structural rearrangements within chromosomes.